BACKGROUND: Immune checkpoint blockade has made a significant impact on the clinical outcomes of patients with metastatic urothelial carcinoma (UC). However, evidence for this approach in patients with non-UC of the urinary tract is limited. METHODS: This was a phase II open-label study of durvalumab 1500 mg and tremelimumab 75 mg every 4 weeks for four cycles followed by durvalumab 1500 mg every 4 weeks. Eligible patients had metastatic non-UC with ECOG PS 0-1 regardless of prior therapy (except small cell carcinoma who were pretreated). The primary endpoint was overall response rate per RECIST v1.1. A Simon's minimax two-stage design was employed, with 13 patients planned for stage one. Pre-treatment tumors underwent PD-L1 staining and next-generation sequencing. RESULTS: Thirteen patients were treated, including seven small cell carcinoma, three squamous cell carcinoma, and three adenocarcinoma. Eleven patients had visceral metastases. No responses were observed; 11 patients had PD and 2 patients had SD. Median PFS was 1.8 months (95% CI, 1.25-not reached [NR]) with a median follow-up of 7.38 months (range, 5.23-21.99 months). Median OS was 6.97 months (95% CI, 4.34-NR). One patient's tumor was PD-L1 positive and all sequenced tumors (n = 8) were microsatellite stable. Grades 3-4 treatment-related adverse events occurred in 38.4% of patients. CONCLUSIONS: In a poor prognosis cohort of patients with non-UC, durvalumab and tremelimumab lacked clinical activity while demonstrating a manageable safety profile.
BACKGROUND: Immune checkpoint blockade has made a significant impact on the clinical outcomes of patients with metastatic urothelial carcinoma (UC). However, evidence for this approach in patients with non-UC of the urinary tract is limited. METHODS: This was a phase II open-label study of durvalumab 1500 mg and tremelimumab 75 mg every 4 weeks for four cycles followed by durvalumab 1500 mg every 4 weeks. Eligible patients had metastatic non-UC with ECOG PS 0-1 regardless of prior therapy (except small cell carcinoma who were pretreated). The primary endpoint was overall response rate per RECIST v1.1. A Simon's minimax two-stage design was employed, with 13 patients planned for stage one. Pre-treatment tumors underwent PD-L1 staining and next-generation sequencing. RESULTS: Thirteen patients were treated, including seven small cell carcinoma, three squamous cell carcinoma, and three adenocarcinoma. Eleven patients had visceral metastases. No responses were observed; 11 patients had PD and 2 patients had SD. Median PFS was 1.8 months (95% CI, 1.25-not reached [NR]) with a median follow-up of 7.38 months (range, 5.23-21.99 months). Median OS was 6.97 months (95% CI, 4.34-NR). One patient's tumor was PD-L1 positive and all sequenced tumors (n = 8) were microsatellite stable. Grades 3-4 treatment-related adverse events occurred in 38.4% of patients. CONCLUSIONS: In a poor prognosis cohort of patients with non-UC, durvalumab and tremelimumab lacked clinical activity while demonstrating a manageable safety profile.
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Authors: Robert M Samstein; Chung-Han Lee; Alexander N Shoushtari; Matthew D Hellmann; Ronglai Shen; Yelena Y Janjigian; David A Barron; Ahmet Zehir; Emmet J Jordan; Antonio Omuro; Thomas J Kaley; Sviatoslav M Kendall; Robert J Motzer; A Ari Hakimi; Martin H Voss; Paul Russo; Jonathan Rosenberg; Gopa Iyer; Bernard H Bochner; Dean F Bajorin; Hikmat A Al-Ahmadie; Jamie E Chaft; Charles M Rudin; Gregory J Riely; Shrujal Baxi; Alan L Ho; Richard J Wong; David G Pfister; Jedd D Wolchok; Christopher A Barker; Philip H Gutin; Cameron W Brennan; Viviane Tabar; Ingo K Mellinghoff; Lisa M DeAngelis; Charlotte E Ariyan; Nancy Lee; William D Tap; Mrinal M Gounder; Sandra P D'Angelo; Leonard Saltz; Zsofia K Stadler; Howard I Scher; Jose Baselga; Pedram Razavi; Christopher A Klebanoff; Rona Yaeger; Neil H Segal; Geoffrey Y Ku; Ronald P DeMatteo; Marc Ladanyi; Naiyer A Rizvi; Michael F Berger; Nadeem Riaz; David B Solit; Timothy A Chan; Luc G T Morris Journal: Nat Genet Date: 2019-01-14 Impact factor: 38.330
Authors: Y Fradet; J Bellmunt; D J Vaughn; J L Lee; L Fong; N J Vogelzang; M A Climent; D P Petrylak; T K Choueiri; A Necchi; W Gerritsen; H Gurney; D I Quinn; S Culine; C N Sternberg; K Nam; T L Frenkl; R F Perini; R de Wit; D F Bajorin Journal: Ann Oncol Date: 2019-06-01 Impact factor: 32.976